Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling (WP3675)

Mus musculus

The signaling pathway that involves insulin-like growth factor 1 (IGF1), and a variety of other components that affect the pathway, plays an important role in the regulation of skeletal muscle growth. The kinase Akt, or protein kinase B (PKB), is a central component in the pathway and is involved in both muscle synthesis, through mammalian target of rapmycin (mTOR) and glycogen synthase kinase 3B (GSK3B), and muscle degradation, through the transcription factors of the FoxO family. The pathway also involves several feedback loops such as the negative feedback of S6K, phosphorylated by mTORC1, which inhibits IRS, or the positive feedback of mTORC2, which is necessary to maximize the activation of Akt. A variety of other factors and pathways also influence the IGF1-Akt signaling pathway at various points. This pathway is based on figure 3 from Schiaffino et al.

Authors

AAR&Co , Alex Pico , Egon Willighagen , Martina Summer-Kutmon , and Kristina Hanspers

Activity

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Organisms

Mus musculus

Communities

Annotations

Pathway Ontology

growth factor signaling pathway insulin-like growth factor signaling pathway signaling pathway

Cell Type Ontology

cell of skeletal muscle

Participants

Label Type Compact URI Comment
SMAD3 GeneProduct ensembl:ENSMUSG00000032402
PGC1 GeneProduct ensembl:ENSMUSG00000029167
FoxO GeneProduct uniprot:Q9R1E0 family of transcription factors
SMAD2 GeneProduct ensembl:ENSMUSG00000024563
AMPK GeneProduct ensembl:ENSMUSG00000029513
Myostatin GeneProduct ensembl:ENSMUSG00000026100
TWEAK GeneProduct ensembl:ENSMUSG00000035678
AKT1 GeneProduct ensembl:ENSMUSG00000001729
Integrin B1 GeneProduct ensembl:ENSMUSG00000025809
TNFrec GeneProduct ensembl:ENSMUSG00000030341
MURF1 GeneProduct ensembl:ENSMUSG00000028834 TRIM63
IRS1 GeneProduct ensembl:ENSMUSG00000055980 not sure, because also 2, 3, 4
PLD1 GeneProduct ensembl:ENSMUSG00000027695
ILK GeneProduct ensembl:ENSMUSG00000030890
PDK1 GeneProduct ensembl:ENSMUSG00000006494
MTOR GeneProduct ensembl:ENSMUSG00000028991 effect of AKT on MTOR is indirect
Part of two multiprotein complexes, TORC 1 and TORC 2
S6K GeneProduct ensembl:ENSMUSG00000020516
TNFa GeneProduct ensembl:ENSMUSG00000024401
PTEN GeneProduct ensembl:ENSMUSG00000013663
IGF1rec GeneProduct ensembl:ENSMUSG00000005533
IGF1 GeneProduct ensembl:ENSMUSG00000020053
Igfbp5 GeneProduct ensembl:ENSMUSG00000026185 most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor
ActRIIB GeneProduct ensembl:ENSMUSG00000061393
mTORC2 GeneProduct uniprot:Q9JLN9 complex of mTOR when bound to rictor
rapamycin insensitive
maximizes activation of AKT1
NFKB1 GeneProduct ensembl:ENSMUSG00000028163
Igfbp1 GeneProduct ensembl:ENSMUSG00000020429 most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor
Igfbp3 GeneProduct ensembl:ENSMUSG00000020427 most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor
Igfbp4 GeneProduct ensembl:ENSMUSG00000017493 most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor
Igfbp2 GeneProduct ensembl:ENSMUSG00000039323 most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor
Igfbp7 GeneProduct ensembl:ENSMUSG00000036256 most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor
Igfbp6 GeneProduct ensembl:ENSMUSG00000023046 most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor
JNK Protein uniprot:Q8BI36

References

  1. Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Schiaffino S, Mammucari C. Skelet Muscle. 2011 Jan 24;1(1):4. PubMed Europe PMC Scholia